Emergency Medicine Forum

A 28 y/o secretary presents with headache. She noted the symptoms were gradual in onset over the past week.  The headache is worse when she is walking, and feels better when she is sitting down or lying down.   The pain is generalized, described as achy, and not associated with any neurologic symptoms of weakness, blurred vision, etc.  The headache is not severe, but seems to be getting worse, and more frequent, so she decided to come and get checked.

ROS:  No fevers documented, but she has felt hot and she has had some chills.  No nausea, vomiting, but she has been anorexic (2-3 lb wt loss over past week).  She has had a sore throat that is mild. Urination and bowl movements are normal. No abdominal pain.  She just finished her period, which are usually heavy.  No chest pain, but she does have a mild cough (dry), and she does get short of breath when she gets the headaches.  This quickly resolves when she rests.  No rashes. 
PMH:  G1P1, no other hospitalizations or medical problems.  No surgeries.
SH:  No smoking, social alcohol use.
FH:  Unremarkable.
Meds:  Ibuprofen for headaches.
PE:  WDWN thin black female in no acute distress.
VS:  HR=110, RR=24, Blood Pressure= 100/50, Temp 99.8F, Sat 95%
HEENT:  Pale conjunctiva, otherwise normal HEENT exam. Neck supple.
HEART: RRR, slightly tachy, no murmurs.
LUNGS:  Equal breath sounds.  Faint rales are heard in RLL.
Abd: Soft, scaphoid, no masses.
EXT: Normal.
Neurologic Exam:  Normal motor, sensory, reflex, cranial nerve, mental status, and cerebellar exam.

Questions:

1. What are the classes of anemia and the most common cause?
 
As anemia is a decreased level of red blood cell mass, the three major ways anemia can occur are:  decreased production, loss of blood, and increased destruction (hemolysis).  The average lifespan of an erythrocyte is 120 days.  (1)

The reticulocyte production index is a calculation of the ratio between the degree of anemia and the response of the bone marrow (reticulocyte production).  It is calculated as follows:

RI= (Retic %/ F) x Hematocrit/Normal hematocrit. 

F is the correction for the longer life span of prematurely released reticulocytes in the blood - a phenomenon of increased red blood cell production.  F is 1.5 if HCT is 25-35% and 2.0 if less than 25%. A free Internet calculator for reticulocyte production index can be found at: http://cpsc.acponline.org/enhancements/227rpiCalc.html

If the index is <2, then the cause is from decreased production of red blood cells.  If the index is > or =2, then the cause is from red blood cell loss (either destruction (hemolysis), or bleeding). (2)

The older method to help differentiate the different types of anemia uses RBC size:  Macrocytic, normocytic, or microcytic. (1) Microcytic anemia is a result of hemoglobin synthesis failure/insufficiency from conditions such as iron deficiency anemia (the most common type of anemia).  Normocytic anemia usually results from acute blood loss, but anemia of chronic disease or hemolytic anemia can also cause it.  Macrocytic anemia is commonly caused by B12 or folic acid deficiency. (3)

2. What type of pneumonia could this be, and why doesn’t beta-lactams work on this organism?  What can help you diagnosis it?  What pattern do you look for on the Chest X-Ray?

Because of the pale conjunctiva (and suspected anemia) and exam consistent with pneumonia, mycoplasma pneumonia should be considered. (4) The anemia would also support the exertional headache and shortness of breath. Other types of pneumonia can also occur (such as Pneumococcal pneumonia, the most common bacteria causing pneumonia in adults), and she may have chronic anemia secondary to heavy periods that are totally unrelated to the pneumonia. In school-aged children, mycoplasma pneumonia is more common.  In preschool aged children, respiratory viruses are the most common. (5, 6)

Mycoplasma pneumonia lacks a cell wall, and therefore is resistant to beta-lactam antibiotics.  Because of this, a macrolide or tetracycline needs to be used. 

Mycoplasma pneumonia infection diagnosis can be challenging, although elevated cold agglutinins can help support the diagnosis. (7) The mycoplasma infection results in the production of auto-antibodies that agglutinate red blood cells at 4 degrees C but not at 37 degrees C.  These cold agglutinins are oligoclonal immunoglobin M (IgM) antibodies that bind the erythrocyte I antigen. (4) Other infections that also produce cold agglutinins include adenovirus, Epstein-Barr virus, and cytomegalovirus. (7) These other infections usually produce cold agglutinins in lower titers (usually less than 1:64).  Mycoplasma infections usually have higher titers of cold agglutinins.  The height of the cold agglutinin response is directly proportional to the severity of the disease. (4) Unfortunately, cold agglutinins may only be elevated in 60% of mycoplasma infections. (8)

The radiographic appearance of mycoplasma infections is variable.  (9)  The most common pattern is a reticulonodular pattern confined to one lobe.  (9). See reference number 5 for an entire manuscript available on the Internet with lots of X-Ray examples of mycoplasma infections. 

Outcome: 

Her Chest X-Ray did reveal a RLL infiltrate, and her hemoglobin returned at only 4gm (the lowest Hbg I’ve ever seen in someone without shock!).  On further questioning, she did admit that the cough may have been around a little longer than only 1 week (it would be very unlikely that she became this anemic that quickly. If she had gone from a Hbg of 11 to 4 in only 1 week, her symptoms would have been much more dramatic).  I ordered the cold agglutinin test, reticulocyte count, and typed and crossed her.  She also got 2 units of blood hung in the ED and 500 mg of azithromycin and 1 gram of Ceftriaxone IV.  Her cold agglutinins came back very positive (next day), and her reticulocyte count was also elevated.  She did recover, and the inpatient team felt the anemia was related to mild hemolysis from Mycoplasma infection, along with significant blood loss from her menses. 

References:
1. Conrad ME.  Anemia.  eMedicine March 11, 2008.  Accessed at: http://emedicine.medscape.com/article/198475-overview
2. Reticulocyte Index.  Wikipedia, accessed at: http://en.wikipedia.org/wiki/Reticulocyte_index
3. Anemia:  Wikipedia.  Accessed at: http://en.wikipedia.org/wiki/Anemia.
4. Atypical pneumonia, Medline accessed at: http://www.nlm.nih.gov/medlineplus/ency/article/000079.htm
5. File TM Jr.  Streptococcus pneumonia and community-acquired pneumonia:  a cause for concern.  Am J Med 2004 Aug2;117 Suppl3A:39S-50S.
6. Ostapchuk M, Roberts DM, Haddy R.  Community-acquired pneumonia in infants and children.  Am Fam Physician 2004 Sep 1;70(5):899-908 Accessed at: http://www.ncbi.nlm.nih.gov/pubmed/15368729?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=5&log$=relatedreviews&logdbfrom=pubmed.
7. Accessed at: http://www.nlm.nih.gov/medlineplus/ency/article/000145.htm.
8. John Mills.  Mycoplasma Infections. Internal Medicine 5th edition.  Stein, JH editor. Accessed at: http://books.google.com/books?id=I_-E-bnauQcC&pg=PA1539&lpg=PA1539&dq=anemia+and+pneumonia&source=bl&ots=bL4b965rGA&sig=hc7USw1ZTvUKYC9NdvGqJ7fWrPM&hl=en&ei=j21gSsGVH4aGtgfKoZnKDA&sa=X&oi=book_result&ct=result&resnum=9
9. Husain MH, Abdulrahman I, Abdulqader B.  Mycoplasma Pneumonia Associated with Severe Autoimmune Hemolytic Anemia. Kuwait Med Journal. June 2004 accessed at: http://www.kma.org.kw/KMJ/Issues/june%202004/Case%20Report/Mycoplasma%20Pneumonia%20Associ.pdf
10. John SD, Ramanathan J, Swischuk LE.  Spectrum of Clinical and Radiographic Findings in Pediatric Mycoplasma Pneumonia. Radiographics 2001; 21:121-131. Accessed at: http://radiographics.rsnajnls.org/cgi/content/full/21/1/121